Device and method for cultivating cells

Abstract

The invention relates to an apparatus for the culture of cells, comprising a mixing apparatus and a reaction space which is bounded by a reactor wall, wherein the reactor wall has at least one connection for the introduction of gas and/or liquid and the reaction space has an internal volume, wherein the reaction space is configured so that the internal volume can be increased by at least 500%, based on a minimum internal initial volume, or that a horizontal cross-sectional area of the reaction space increases from the bottom upward. The invention further relates to a process for the culture of cells.

1 . An apparatus for the culture of cells ( 10 ), comprising a mixing apparatus ( 12 ) and a reaction space ( 14 ) which is bounded by a reactor wall ( 16 ), wherein the reactor wall ( 16 ) has at least one connection ( 18 ,  20 ) for the introduction of gas and/or liquid and the reaction space ( 14 ) has an internal volume ( 15 ), wherein the reaction space ( 14 ) is configured so that the internal volume ( 15 ) can be increased by at least 500%, based on a minimum internal initial volume, or that a horizontal cross-sectional area ( 42 ) of the reaction space ( 14 ) increases from the bottom upward. 
     
     
         2 . The apparatus as claimed in  claim 1 , characterized in that the reactor wall ( 16 ) comprises an extensible material, where the extensible material has an extensibility of at least 200% and/or the reactor wall ( 16 ) has a first part ( 16 . 1 ) and a second part ( 16 . 2 ), where the first part ( 16 . 1 ) is arranged movably and with a sealing connection relative to the second part ( 16 . 2 ). 
     
     
         3 . The apparatus as claimed in  claim 2 , characterized in that the extensible material contains natural rubber, synthetic rubber, polyisobutylene, silicone rubber or mixtures thereof. 
     
     
         4 . The apparatus as claimed in any of  claims 1  to  3 , characterized in that the minimum internal initial volume is in the range from 2 ml to 1 l and can be enlarged to a maximum internal volume of from 10 l to 100 l. 
     
     
         5 . The apparatus as claimed in any of  claims 2  to  4 , characterized in that the at least one connection ( 18 ,  20 ) for the introduction of gas and/or liquid is conducted through the extensible material of the reactor wall ( 16 ). 
     
     
         6 . A process for the culture of cells in an apparatus as claimed in any of  claims 1  to  5 , comprising the following steps:
 a. optionally sterilization of the reactor wall ( 16 ) at a temperature of from 80° C. to 150° C. or by means of gamma radiation, 
 b. charging of the apparatus, with cells ( 29 ) and optionally a first liquid medium being introduced into the reaction space ( 16 ), 
 c. metering of a second liquid medium ( 26 ) and/or a gas into the reaction space ( 14 ), with the second liquid medium preferably having a composition which corresponds to that of the first liquid medium ( 26 ), and
 enlargement of the internal volume ( 15 ) of the reaction space ( 14 ) by at least 500%, based on the minimum internal initial volume, or 
 enlargement of a fill height in the reaction space ( 14 ), whose horizontal cross-sectional area ( 42 ) increases from the bottom upward, with a volume of a liquid phase ( 28 ) in the reaction space ( 14 ), which comprises the second liquid medium ( 26 ) and optionally the first liquid medium, increasing by at least 500%, based on a minimum liquid initial volume. 
 
 
     
     
         7 . The process as claimed in  claim 6 , characterized in that the reactor wall ( 16 ) comprises an extensible material and the extensible material is extended in step c) and/or the reactor wall ( 16 ) has a first part ( 16 . 1 ) and a second part ( 16 . 2 ) and the first part is moved relative to the second part ( 16 . 1 ) in step c). 
     
     
         8 . The process as claimed in  claim 6  or  7 , characterized in that the second liquid medium ( 26 ) is introduced continuously and/or stepwise. 
     
     
         9 . The process as claimed in any of  claims 6  to  8 , characterized in that the cells ( 29 ), the second liquid medium ( 26 ) and optionally the first liquid medium are mixed in the reaction space ( 14 ). 
     
     
         10 . The process as claimed in any of  claims 6  to  9 , characterized in that the liquid phase ( 28 ) occupies from 10% by volume to 80% by volume of the internal volume ( 15 ) before and after the metered introduction in step c). 
     
     
         11 . The process as claimed in any of  claims 6  to  10 , characterized in that the cells ( 29 ) are present in a suspension culture in the reaction space ( 14 ).